Orbital Welding Technology for Pharmaceutical Piping Systems

Orbital welding technology for pharmaceutical piping systems

Figure 1. Orbital welding operators installing a stainless steel piping system in a pharmaceutical plant in the UK. (Photo courtesy of A.T.W. Services)

The capability of making a
smooth, crevice-free inner weld bead on a repeatable basis, has led, over the
past decade, to orbital welding becoming the preferred joining technology for
biopharmaceutical process piping.

The expanding biopharmaceutical industry in the USA has placed an increasing
emphasis on quality standards and documentation in order to expedite the
approval process for new therapeutic products by the FDA (United States Food
and Drug Administration).

The approval process requires that the facility in which a new drug is produced
must be designed, constructed and commissioned so that it meets the criteria for
process validation. Failure to achieve validation on the first attempt can be
very costly to the facility owner, so maintaining quality from the design phase
throughout the construction process is essential. The quality inherent in
orbital welding joining technology is consistent with the goals of the CGMP
(Current Good Manufacturing Practices) for achieving hygienic pharmaceutical
piping systems that will have no adverse affect on the products that pass
through them.

Validating
critical process systems

In validating the critical process systems in a new or modified facility, the
FDA will seek to determine whether the requirements of three key documents, the
CGMP, the ASME (American Society of Mechanical Engineers) B.31.3 Process Piping
Code, and the project specifications have been met.1

Of these documents, the most significant is 21 CFR (Code of Federal
Regulations) B211 which specifies how the various components in pharmaceutical
manufacturing facilities are to be constructed. 21 CFR B211.65 Subpart D
states:

(a)
Equipment shall be constructed so that surfaces that contact components,
in-process materials, or drug products shall not be reactive, additive or
absorptive so as to alter the safety, identity, strength, quality, or purity of
the drug product beyond the official or other established requirements.

The FDA is very non-specific about
how a critical piping system should be constructed, but relies upon the
requirements detailed in the ASME B31.3 Process Piping Code and the ASME
Bioprocessing Equipment Standard (BPE-97). It should be noted that a code is
required by law, while a standard provides generally accepted industry
practices.

The ASME B31.3 Process Piping Code gives to the owner the ultimate responsibility
for documenting to the FDA that the critical piping systems have been
manufactured, fabricated, and installed according to the CGMPs.

Welding is an important aspect of piping system design and fabrication. ASME
B31.3 provides acceptance criteria for welds (Table 341.3.2), details the types
of examinations required, the number of welds to be inspected, and establishes
qualifications for welding inspectors. In 1989, representatives of the emerging
bioprocess industry came together with the realisation that existing standards
did not adequately meet the need for design and construction of equipment to be
used in critical bioprocess piping systems. A consensus was reached on the need
for equipment design that would be both cleanable and sterilizable. Special
emphasis was placed on the quality of weld surfaces once the required strength
was present. The ASME published the ASME Bioprocessing Equipment Standard
(BPE-97) in 1997.

Figure 3. Recent recommendations call for reduced deadleg L/Ds to improve cleanability and sterilisability. Orbital welding is ideal for this application, as shown on this orbital weld of a short sanitary ferrule to a pulled tee.

ASME
BPE-97. Qualification to ASME BPE-97 requires that welds be certified to ASME
Section IX of the Boiler and Pressure Vessel Code and ANSI/ASME B31.3 Process
Piping. This requires that a Q.A. manual and a Q.A. program be in effect with a
set of weld standards which reference the BPE Standard. ASME Section IX is done
to verify the structural integrity of the weldments. To meet this requirement
sample welds are subjected to bend tests to verify weld ductility, and tensile
testing is done to assure that welds meet the minimum tensile strength
specified for the base material. The results of these tests are documented as
part of the WPS (Weld Procedure Specification) Form QW-482*, and the PQR
(Procedure Qualification Record) Form QW-483*. Welders and welding operators
may be qualified by making acceptable test welds and documenting test results
on Form QW-484*. Welder tests require six linear inches of weld or multiple
coupons, but not more than four.

It should be noted that hot WFI water, circulated at temperatures above 40ºC,
may be classified as category M fluid service in ASME B31.3, which includes
substances which will do irreparable harm in case of a piping system failure in
which the contained process fluid comes into contact with human tissue. Weld and
inspection criteria for this category are more stringent than for normal fluid
service. 21CFR B211.65, Equipment Construction and B211.67, Equipment Cleaning,
state that the materials used must be suitable for their intended use which
would include the ability to withstand high temperatures and pressures as well
as the ability to hold up to sterilising and sanitising agents. Clearly,
orbitally welded stainless steel meets these criteria.

While ASME B31.3 was written with manual welding in mind, ASME BPE-97
recommends the use of orbital or machine welding for bioprocess piping. Manual
welding may be used, with the owner’s permission, only when using an orbital
weld head would create a deadleg. A deadleg is defined as a pocket, tee, or
extension from a primary piping run that exceeds a defined number of pipe
diameters from the I.D. of the primary pipe.

In ASME BPE-97 (Table SD-1) a deadleg (L/D) of 2:1 is considered to be an
achievable target value for bioprocessing systems where L is the length of the
extension measured from the OD of the primary pipe, and D is the I.D. of the
extension. Deadlegs are undesirable because they are difficult to clean and
maintain in a sterile condition and may represent an unacceptable bioburden to
the system. Where they exist, they should be designed so that it is possible to
flush through them.

The intelligent use of orbital welding technology can help to keep deadlegs to
the required minimum. Some orbital weld heads have provisions for locating the
tungsten electrode close to the edge of the head to accommodate parts with
short "stick-outs" such as welding short sanitary ferrules to stubs
on transfer panels or to pulled tees, as shown in Figure 3. Narrow weld heads
are now in use with reduced axial clearances that make it possible to orbitally
weld fittings-to-fittings that could not be welded with standard weld heads.

For areas with limited radial clearances it is important to use a weld head
that is as small as possible for the tubing being welded. Contractors tent to
use a single weld head to accommodate all sizes from 1 inch to 4 inches, which
is practical for most situations. However, some of the joints on smaller tube
sizes that have inadequate radial clearance for a large weld head might be
accessible with a smaller weld head. In designing piping systems, allowances
should be made to allow for placement of orbital weld heads and eliminate
insofar as possible the need for manual welds.

The
International Society of Pharmaceutical Engineers is publishing a series of
ISPE Baseline Guides developed by ISPE in cooperation with the FDA to establish
a baseline approach to new and renovated facility design, construction
commissioning and qualification. The intent is to document current industry
practice for facilities and systems used for production of pharmaceutical
products and medical devices and to avoid unnecessary spending on facility
features that have no impact on product quality. Volume 4: Water and Steam
Guide recommends the use of orbital welding for the installation of
pharmaceutical water systems, citing the smooth inner weld bead.4

The ASME BPE-97 Standard recognizes the importance of the surface quality of
welds for maintaining the cleanability and sterilizability of piping systems. A
smooth internal surface finish of the piping system, including the welds, is
important for controlling the buildup of biofilm that could contaminate the
product.

The Materials Joining part of ASME BPE-97 requires that the weld criteria of
ASME B31.3 which prohibits weld discontinuities such as cracks, voids,
porosity, undercut, lack-of-fusion, and incomplete penetration that would
affect the structural integrity of welds be met but, in addition, provides
visual weld criteria that are important for maintaining the hygienic condition
of the piping system.

Welds must be fully penetrated with good alignment, with a flat OD and ID
profile. An unpenetrated weld has a crevice which may not be reached by CIP
cleaning and becomes a refuge for bacteria. Excessive I.D. concavity,
convexity, or misalignment, that could interfere with proper draining of the
system and allow pooling of fluid where bacteria could gain a foothold presents
an unacceptable bioburden to the system.

Discoloration of the weld

Any discoloration of the weld or HAZ as a result of oxidation during welding
must be held to a minimum. A light discoloration may be permissible if it is
tight to the surface, but the amount allowed (if any) for a particular
installation is subject to agreement between the owner/user and the contractor.
Discoloration has been shown to be proportional to the amount of oxygen (and
moisture) in the ID purge gas which is usually argon. A cryogenic source (dewar
or bulk gas supply) is recommended for urging during welding of high purity
pharmaceutical water systems.

Oxygen concentrations in the low parts per million range in argon will usually
produce welds with light or no discoloration assuming the purge time is
sufficient and there are no leaks in the purge system. Purifiers are available
that bring the oxygen (and moisture) levels to the low parts per billion (ppb)
range which will usually, but not always, produce welds with no visible
discoloration. Purge procedures, including flow rates used on specific weld
heads and for ID purges, specified levels of argon purity, and discoloration
criteria for welds are detailed in the project specification that is prepared
by the architect engineering firm and the contractor in advance of
construction.

In validating a piping system, the most important determinants of water quality
monitored by the FDA are the (live) bacterial count and endotoxins which are
produced from (dead) bacterial cell walls.8 Full-penetration
crevice-free welds with a smooth I.D. surface are important for meeting these
qualifications.

Inspection
and documentation

Figure 5. AMI Model 8-4000 weld head welding a stainless steel elbow to a tube. This narrow weld head provides reduced axial clearances, increasing the number of joints that can be accommodated with orbital welding equipment. This head is water-cooled to permit a high duty cycle.

An inspection plan detailing the types of examinations to be made shall be
agreed to in advance of the job by the owner/user and contractor. ASME BPE-97
requires that all welds be inspected visually on the OD, and that a minimum of
20% be selected at random for internal inspection with a borescope. The reject
rates for orbital welding in biopharmaceutical applications have been extremely
low.

By refining their standard operating procedures which are detailed in the
project specifications, mechanical contractors have documented reject rates for
orbital welding as low as 0.2%. The ASME BPE-97 Part SD Design for Sterility
and Cleanability lists the kinds of documentation that may be used to verify
conformance with sterility and cleanability. The kinds of documentation shall
be agreed to at the outset of a design project by the owner/user and the
manufacturer (installing contractor).

Figure 6. Weld schedule print-outs can be used as part of the weld procedure documentation package.

It would also include detailed instructions for receiving, inspection of
incoming materials, fabrication, cutting, end-preparation, cleaning of weld
components and provision for a clean area set aside for welding. Tracking of
tubing material heats and control of diameters and wall thicknesses for
specific applications should also be defined.

This information would be detailed in the project specification listed in ASME
BPE-97 Part SD Design for Sterility and Cleanability shall also be retained by
the owner/user for a period of at least three years.

Corrosion
resistance of orbital welds

Validation of a piping system for high purity water proceeds in three phases:
1) at system start-up, 2) when the system is up and running, and 3) after a
period of operation of about a year. Water samples must be collected and
analysed at specified intervals to demonstrate that the system produces water of
acceptable quality on a continuous basis.

Weld quality is most important for the long-term successful operation of the
system. Rouging, a form of corrosion sometimes associated with welds in
pharmaceutical piping systems, is fairly common and may affect water quality.
When properly welded with an adequate purge of the joint I.D. and passivated
after welding, orbital welds on 316L stainless steel have pitting potentials
equivalent to those of unwelded tubing which is indicative of good corrosion
resistance.5

Use of orbital welding in biopharmaceutical industry

Orbital welding, which uses the GTAW process, is used in the biopharmaceutical
industry for piping systems which have direct or indirect contact with the
product and may also be used for other, less critical, systems. These include
WFI (water for injection), clean steam, and product lines. It is also used for
connecting tanks and vessels to the piping systems, in construction of
equipment such as multi-effect stills, and to connect bioprocess equipment
mounted on skids.

Typical tubing diameters for biopharmaceutical applications are 1 to 4 inches
OD, but 1/2 inch OD tubing for instrumentation tubing supplying bioreactors was
welded orbitally by B. Braun Biotech. Autogenous welds up to 7 inches in diameter
can be done in enclosed orbital weld heads, but larger tube and pipe sizes
require the use of orbital welding equipment with filler wire capabilities.

Power supplies are microprocessor-controlled. The weld parameters controlled by
the power supply include primary and background welding currents, pulse times,
rotor travel speed (RPM), level times, rotation delay, and purge times. These
are recorded on a weld schedule for each size and wall thickness of tube or
pipe and stored in the power supply memory. They are easily recalled for
welding and the schedules can be modified for different heats of materials or
for tube-to-fitting welds and the changes stored in memory as needed.

Print-outs from the power supply may include the weld identification number,
the operator’s name, and the serial numbers of the power supply and the weld
head. This information can be used in conjunction with the welding log as part
of the documentation package.

The use of orbital welding is expanding in Latin America. Fiocruz Instituto de
Tecnologia em Imunobiologicos used orbital welding in the fabrication of a new
building used for the manufacture of vaccines. Orbital welding was used for
joining the WFI piping, the DI loop piping, as well as service piping for cold
water, air, and steam systems. Type 316L stainless steel tubing was used for
both WFI and DI water systems. Cold water is used for washing glassware used in
the plant, hot DI water is used for rinsing the glassware, and air for drying
it.

Engineering contractor, Termo Engenharia Ltda, wanted to upgrade its welding
procedures and standards to a level that would satisfy the FDA in the USA since
Fiocruz intended to export its products. The installation was very successful
and Fiocruz is planning to use orbital welding on another new facility at the
same location.

Other Latin American pharmaceutical users of orbital welding include Schering
do Brasil, and orbital welding is being used in plants for the manufacture of
cosmetics and other hygienic applications such as breweries, dairies and juice
packagers throughout Latin America.

Productivity

Productivity is typically higher for orbitally welded systems than for
comparable manual installations. Productivity gains are achieved through
reduced time to weld each joint as well as lower reject rates and reduced need
for rework. Thus orbital welding is eminently suitable for
"fast-track" construction projects without sacrificing quality.

Summary

During validation, the FDA will examine all the documentation to make certain
that procedures outlined in the project specification have been followed and
properly documented in accordance with the CGMP. Orbital welding done in
compliance with the ASME Bioprocessing Equipment Standard, which by reference
includes ASME B31.3 Process Piping and ASME Section IX of the Boiler and
Pressure Vessel Code, is a key component in achieving pharmaceutical piping
system validation in a timely manner.

The repeatability of the process makes it possible to achieve crevice-free
welds with a smooth surface that can be maintained in a clean and sterile
condition on a routine basis. The smoother surface decreases the affinity for
colonization and growth of microorganisms and increases the efficacy of CIP.

Similarly, the controlled heat input of orbital welding combined with the use
of proper purging technology and passivation results in welds that are
comparable in corrosion resistance to unwelded base materials. Thus orbitally
welded systems, installed with proper fabrication techniques and documentation,
are in compliance with 21 CFR B211 Subpart D facilitating piping system
validation as well as providing excellent performance in service.